A compound of formula I, hereinafter, and its pharmacologically acceptable salts, esters and amides has been used successfully in the prophylactic treatment of asthma for many years. One particular compound, commonly known as cromolyn (formula II, hereinafter), is routinely used as a prophylactic treatment for asthma, rhinitis, conjunctivitis and intestinal masocytosis. These compounds do not alleviate the symptoms of asthma once an attack has begun.
Cromolyn is not a bronchial or vaso dilator as is usual for asthma treatments. Rather, cromolyn acts to inhibit the release of inflammatory mediators such as histamine from several types of cells in the lungs. Inhalation of a solution containing the disodium salt of cromolyn (cromolyn sodium), on a regular schedule by an individual suffering from asthma provides a prophylactic treatment for bronchial asthma. The prophylactic response increases with the length of use of the drug.
A chromone compound corresponding to formula I and its pharmacologically acceptable salts, esters and amides has also been reported to be effective against certain atopic skin disorders such as atopic eczema and various other chronic skin conditions that involve skin mast cells and/or an antibody-antigen reaction. (Sullivan U.S. Pat. Nos. 4,362,742 and 4,271,182).
Skin conditions of the type discussed in Sullivan (atopic dermatoses) are systemic skin diseases that do not result from exposure to an externally introduced allergen, but rather are believed to have internal causative factors. These conditions are also known or suspected to have hereditary causation or predisposition. Outbreaks of skin lesions occur periodically throughout life, often beginning in early infancy.
One common and effective treatment of the lesions associated with atopic dermatoses is topical application of corticosteroids. Oral steroids can also be given in severe cases. However care needs to be taken when using steroids for atopic dermatoses since there is often a rebound reaction when the steroid treatment is stopped.
Topical antihistamines have not been found to effective. However, the itching associated with the lesions may be relieved by large doses of oral antihistamine (for example, diphenhydramine 50 mg b.i.d or q.i.d. for adults).
Topical treatment of the lesions associated with atopic dermatosis with a compound corresponding to formula I or its pharmacologically acceptable salts, esters or amides has been shown to facilitate healing of the lesion being treated. However, treatment does not actually cure the disease itself.
Chromone compounds have also been shown to be effective against certain allergic conditions of the eye.
However, chromone compounds corresponding to formula I are not predictably or uniformly absorbed by all types of tissue and the effectiveness of these compounds against other conditions of the skin or epidermis is not predictable.
The exact mechanism of action of a chromone compound is unknown. A chromone compound is believed to possess no vasodilator, antihistaminic or anti-inflammatory activity. It is known that a chromone compound, and particularly cromolyn, is poorly absorbed by the lungs and by the gastrointestinal tract. Only about 7-8 percent of a usual total dose is absorbed from the lung, and is then rapidly excreted, unchanged, in the bile or urine. The remainder is expelled from the nose or, if swallowed, excreted by the alimentary tract.
An immediate hypersensitivity reaction, also known as a Type I hypersensitivity reaction or a Type I reaction, can occur after exposure to an allergen. Type I hypersensitivity reactions of the skin, or cutaneous Type I hypersensitivity reactions, are often the result of insect bites or stings, but can also result from exposure to other substances to which the patient is sensitive, such as latex or the saliva of an animal.
All Type I hypersensitivity reactions are characterized by a rapid response to exposure to an allergen. Physical manifestations and symptoms of the reaction typically occur between 1 and 15 minutes after exposure.
The physical manifestations and symptoms, of a cutaneous Type I reaction, can include swelling of the affected area, reddening of the skin, and mild to severe pruritus in the area directly exposed to the allergen as well as the immediate surrounding area.
Immunologically, the body upon exposure to the allergen produces IgE antibodies that bind to the surface receptors of mast cells and basophils. Upon re-exposure to the allergen, the allergen bonds to the cell-associated IgE, causing signal transduction in the mast cells and basophils and secretion of mediator. The mediator then acts upon body structures resulting in the observed physical reaction.
In Type I reactions, the pathology is related to degranulation of mast cells and the reaction caused by mediators such as histamine and leukotriene C4 (LTC4).
If left untreated, most symptoms caused by Type I hypersensitivity reactions gradually subside and then go away entirely. The time required varies considerably from individual to individual.
During the time the reaction and symptoms persist, the individual is uncomfortable, often intensely uncomfortable. If untreated, the affected area in a cutaneous Type I reaction is frequently scratched or rubbed raw. This action can result in secondary infection at the site and scarring in some instances.
There have been numerous remedies utilized for the itching caused by cutaneous Type I reactions. Topical remedies include calamine lotions, baking soda, steroids and a variety of "home" remedies. Topical as well as oral antihistamines are also often used to lessen the discomfort caused by Type I reactions. These remedies have demonstrated varying degrees of effectiveness.
Currently, prevention of a Type I reaction requires avoidance of the allergen or a participation in a desensitization program that is not always effective and generally requires years of treatment.
Although Type I reactions generally, and cutaneous Type I reactions specifically, are not usually life-threatening or dehabilitating, they do cause discomfort and at certain times of the year can occur quite often. It would therefore be advantageous to be able to prevent and effectively treat these types of reactions with a simple topically applied remedy. Disclosure of one such remedy is as follows.